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Optogenetic System and Method

Active Publication Date: 2019-06-06
UNIVERSITY OF NEWCASTLE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides an optogenetic system for preventing or halting seizures in a neural network by using an optical stimulator to deliver an excitatory stimulus to target neurons, based on an input signal from a sensor monitoring the neural network. The optogenetic system aims to reduce the overall activity of the target neurons, which may be associated with seizures or seizure-like events, and thus prevent or halt seizures. This technology offers the advantage of being able to measure and stimulate the neural network simultaneously, unlike other electronic techniques which disrupt the network.

Problems solved by technology

In “electronic only” systems, the application of electronic stimuli cannot be performed at the same time as measurement using the same electrodes, due to the disruption caused.

Method used

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Examples

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example 1

endent Modulation of In Vitro Epileptic Activity Using Closed-Loop Optogenetic Stimulation

[0097]This example considers phase-dependent modulation of epileptic activity using closed-loop optogenetics in rodent brain slices selectively expressing Channelrhodopsins-2 (ChR2) either in excitatory pyramidal neurons using an Emx1 promoter, or in a subset of inhibitory cells using the parvalbumin (PV) promoter.

Experimental Details

[0098]Brain Slice Preparation

[0099]Coronal neocortical brain slices (400 μm) were prepared from Emx1-ChR2 and PV-ChR2 mice, which provides selective neuronal expression of channelrhodopsin-2 in glutamatergic cells (Gorski et al., 20021). The mice were perfused using the same ice-cold oxygenated (95% O2 / 5% CO2) sucrose-containing artificial cerebrospinal fluid (sACSF) used for cutting the brain slices; (sACSF in mm: 252 Sucrose, 24 NaHCO3, 2 MgSO4, 2 CaCl2), 10 glucose, 3.5 KCl, 1.25 NaH2PO4). Rodent brain slices were cut using a 5100 mz vibratome (Camden Instrument...

example 2

endent Modulation of in Silico Epileptic Activity Using Closed-Loop Stimulation

[0121]This example considers computational modelling work that parallels the in vitro closed-loop optogenetic stimulation experiments discussed above.

[0122]Methods

[0123]Modelling Epileptiform Activity

[0124]The model used here is a variant of the classic Wilson-Cowan neural population model [Wilson and Cowan, 19723], which is described in detail in previous publications [Wang et al., 2012, Wang et al., 20144]. The two-variable version of it is used, which models the neural tissue as a single excitatory population and a single inhibitory population. This model is able to capture epileptiform spikes and epileptiform discharges [Wang et al., 20125], which are the two key activity types from the experimental data. 3Wilson, H. and Cowan, J. (1972). Excitatory and inhibitory interactions in localized populations of model neurons. Biophysical Journal, 12(1):1-244Wang, Y., Goodfellow, M., Taylor, P. N., and Baier,...

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Abstract

An optogenetic system and method for preventing or halting seizures. The system and method use a sensor for monitoring the activity of a neural network containing a group of target neurons, and generating an input signal indicative of said activity, the target neurons being excitatory neurons. Excitatory stimulation is delivered in the form of an optical signal by an optical stimulator to the target neurons, the optical signal being determined based on the input signal, to reduce the overall activity of the target neurons.

Description

FIELD OF THE INVENTION[0001]The present invention relates to an optogenetic system for the halting or prevention of seizures, a control device for use in such a system, and a method of halting or preventing seizures.BACKGROUND OF THE INVENTION[0002]The brain is made up of around 100 billion neurons, which are responsible for transmitting signals throughout the body, in the form of propagating electrical pulses. These pulses propagate in the form of an action potential. Action potentials arise when a threshold potential difference is applied across the neuron membrane (also referred to as a membrane potential), and are seen as a spike in the potential difference across the membrane, i.e. a rapid depolarization. Prolonged stimuli, rather than affecting the amplitude or duration of an action potential, instead result in a series of identical action potentials, the frequency of which depends on the intensity of the stimulus. When an action potential is generated in a neuron, this may be...

Claims

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Application Information

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IPC IPC(8): A61N5/06A61B5/0478A61B5/00
CPCA61N5/0622A61B5/0478A61B5/4094A61N2005/0612A61B5/6868A61B5/01A61B5/4836A61B5/291A61B5/293
Inventor JACKSON, ANDREWCUNNINGHAM, MARKBAKER, STUARTDEGENAAR, PATRICK
Owner UNIVERSITY OF NEWCASTLE
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